Hello, everyone, and welcome to day 3 of the 2021 Bank of America Health Care Conference. Thank you for joining this session with NextCure. My name is Alex Stranahan, and I'm the analyst covering NextCure here at BofA. I'm pleased to be joined with joined by Michael Richmond, the President and CEO of Nexmosphere.
And I believe Michael has been brought through some slides to start, and then we can jump into q and a if there's time. So that's Michael over to you.
Great. Well, thank you very much, Alec, and thank you very much for the opportunity to speak at the BofA Securities Conference. It's a pleasure to give you a quick update on NextGear. So hopefully everyone has the slides in front of them. The first slide really addresses the key vision for the organization and this involves developing next generation immunomedicines.
On Slide 2 is our forward looking statements. On Slide 3, these are NextGear's highlights. We call these the 3 Ps, our pipeline, our platform and people. I'll walk you through quickly our pipeline. We're very proud of it over the last 5 years.
We've introduced 3 INDs, taken 2 products into the clinic, NC318, which is currently in Phase 2, NC410 currently in Phase 1, and a recently announced IND filing of NC762. In addition to the pipeline, we have a discovery platform we call FIND IO. This stands for functionally investigated investigator discovery in immuno oncology. And this enables us to discover and validate novel targets that we hope will impact those patients in need and addressing unmet medical need. And then finally, our people.
We have a fully integrated GMP manufacturing facility that's to produce clinical material to support our pipeline. We've recently announced earlier this year the hiring of Doctor. Han Mint as our CMO. And then finally, as many of you may recall, the company was discovered was founded about 5 years ago, whereby Doctor. Liping Chen, who discovered PD L1 and remains fairly active with the company as both a founder, consultant and Head of our Scientific Advisory Board.
Slide 4 is a high level overview of our product development pipeline. NC31 is a humanized monoclonal antibody against SIGLIT-fifteen. We're currently in Phase 2 in monotherapy. We've also recently announced a combination with PD-one with our founding institution at Yale University. Thirdly, we're pursuing a Phase 1 clinical trial.
This is a dose escalation safety tolerability study with NC410 or layer 2 decoy program. And then finally, NC762, which will be initiating clinical trials shortly. In addition to that, we have multiple programs working their way through the pipeline and you'll be hearing much more about those in the coming years. Just to point out, NextGear owns full worldwide rights to each of its programs. So Slide 5, let's briefly talk about NC-three 18.
This is a humanized monoclonal antibody targeting SIGLIT-fifteen. SIGLIT-fifteen was in fact discovered by Liping Chang at Yale University. It's got a unique expression profile unlike many other IO targets since it's expressed both on the tumors and the infiltrating M2 macrophages. This unique expression profiles creates an immunosuppressive environment and we've developed NC318 to counteract desuppression and to activate the immune cells to kill the tumor. I will briefly talk about an update on the program with respect to our newly developed CLIA validated immunohistochemistry test that we'll be using for selecting patients.
We recently announced our collaboration with our founding institution at Yale University to return to lung with respect to looking at both monotherapy and combination with an anti PD-one. And we'll be applying a lot of the lessons we've learned with respect to patient selection, looking at combinations and also addressing an extensive biomarker analysis with our future programs. So just to kind of recap for those that have been following the company, you may recall NC31's history in Phase 1 where we had we conducted a dose escalation study, 49 patients, 15 different tumor types. We looked at all comers at the time. At that time, about 25% of those patients were non small cell lung cancer.
We had 1 CR, we had 1 PR and 3 stable disease. Happy to say that the CR and PR subjects remain on therapy. Our Phase II, which is ongoing, the recommended Phase II dose at 400 mgs every 2 weeks, We're conducting biopsies and we've announced in the past that we have 2 PRs, 1 in head and neck, 1 in triple negative breast, both in which we've advanced to the stage 2 of the SIMON2 stage study. Moving forward, we'll be selecting for S15 positive patients. As mentioned earlier, we're also conducting a study with Roy Herbst and Scott Gettinger at Yale.
These are leading lung cancer oncologists, and we're very fortunate to have the opportunity with them coupled with the supply of pembro by Merck. This is a 3 arm study, a mono study looking at its 15 positive patients in a PD-one refractory setting. And then quite interestingly looking at the combo with pembro both in PD-one refractory and PD-one naive patients. I think 1 of the more important updates and something many of you know we've been working on for a long time is a clear validated immunohistochemistry test. So this is a highly specific sensitive monoclonal antibody that helps us detect S15 expression in patients both on the tumor and within the stroma.
So we'll be taking tumor biopsies from patients. We'll be validating those with our clear validated test and enriching for selection for S15 positive patients moving forward. And we'll be reporting an update on this trial by the end of this year. Let me transition into MC410, our 2nd program. So this works through a decoy mechanism involving LARE-one and LARE-two.
Layer 1 is a co inhibitory molecule expressed on dendritic cells and T cells that creates this negative signaling and immunosuppressive condition. And what we've tapped into is what mother nature does naturally. She created a second gene called LARE 2, which is much more specific to the ligands than LARE 1 and shuts down that inhibitory response that enables 1 to restore immune function. Quite interestingly, the mechanism of action works through the extracellular matrix. So we believe this interaction is having an impact on changing the architecture of the ECM moving forward, which will hopefully restore immune function and treat patients.
At SITI last year, we had 2 posters with respect to the mechanism of action in NC410 and also looking at combination therapies and 3 independent preclinical experimental works with respect to looking at PD-one and PD L1 combinations. And we'll have an upcoming poster at ASCO with respect to kind of an in trial in progress. Mechanistically, a LIR-one and LIR-two bind 1 of 2 ligands, both collagen on the tumor as well as C1q, which is part of the complement pathway. Layer 2 competes with Layer 1 to restore immune function. And what we've done is we've just basically taken what we've learned from mother nature.
We've created a bio mimic of layer 2, which enables us to outcompete layer 1 binding to activate T cells in dendritic cells to kill the tumor. As mentioned earlier, we're currently in the Phase 1 portion of a Phase onetwo human study. This is a dose escalation and safety and tolerability study. We're looking at multiple advanced and metastatic solid tumors. Most of these tumors are fairly collagenous based since layer 1 and layer 2 bind collagen within the extracellular matrix.
So we're looking at long ovarian and pancreatic as well as other tumor types. So we'll be providing an update on the Phase 1 trial by year end. Transitioning into our 3rd program, again within 5 years is NC762, this is a humanized monoclonal antibody against B7 H4. We screened and evaluated many antibodies to develop this particular candidate that has a unique mechanism of action in directly killing tumors that is independent of T cells. NK cells have been shown to enhance this tumor activity and we've been looking and our plan is to look at a number of gynecological cancers as well as lung cancer moving forward where we know B7 H4 is heavily expressed.
So the IND is filed, unique mechanism of action. Many lessons learned from NC-three 18, so we will have an assay as we will with NC-four 10 to select those patients that express the target that we believe will have be most responsive to treatment. And we'll be evaluating extensively biomarkers. I'd like to just touch base on our manufacturing. It's not something we often talk about, but a critical and competitive advantage, especially during the time of COVID, where it's difficult to get biologics manufacturing capacity.
We had 1, 000 liters of capacity during COVID over the last year. We doubled that capacity by adding another bioreactor. This provides an efficiency that enables us to produce clinical material much more quickly than outsourcing that others might do. Also provides us a lot of flexibility in scheduling, efficiency from an operation and capital use perspective and then also managing the quality of the clinical material that we produce. All 3 of our trials will be using clinical material produced here at NextEra.
And then finally, we have our platform. Again, this is Find. Io, functional integrated Next Tier Discovery. This is a platform that we industrialized, automated and roboticized from what's Leaping originally developed and how we discovered PD L1. And we're applying these screens and these validation tools to develop this whole next generation.
And you'll be hearing about a lot of these targets working their way through the pipeline. Independent of oncology, there are opportunities to diversify into other areas such as autoimmunity and inflammation and also neuro as it relates to the targets that we've been discovered. Anticipated near term milestones on Slide 15, as mentioned earlier, we'll provide an update by year end for on both the NC318 Phase II trial as well as the NC410 Phase I study. Q2 of next year, we'll be focusing on the outcome of our collaborative work with Yale looking at the mono and combo studies with NC318. And then Q2 of next year, we'll provide an update on the NC76 2 study.
So thank you very much for the opportunity to give a brief update. And just in summary, Nexcare has taken a very focused approach over the last 5 years. We have a lot of momentum. We've taken 3 things pretty much in the clinic, leveraging our platform and applying all this to develop next generation Immunomedicine. So thank you, Alec.
Great. Thanks, Michael, for that overview. Very helpful. So now we can transition to Q and A. I have a few here, but for those dialed into the webcast to log a question, simply submit it to the Veracast platform and I'll read it off.
But Michael, maybe we can just start on NC318. So we obviously saw some early responses from the Phase 1 and the Phase 2 study is ongoing. Could you maybe talk about the F-fifteen patient selection you're planning to implement, think starting in 2Q? This is active already. And I guess, could you just talk a little bit about the assay that you've built?
Sure. It's a great question. So what we've learned in developing this next generation immunomedicines is that when you're looking at novel targets and 1st in class proprietary molecules, there are 3 things we have to get right, the target, the candidate and the patient. So focusing on the patient, we've realized and there's been some learning lessons along the way how important patient selection is. So we're planning moving forward at the end of this quarter to continue with the Phase 2 enrollment is we've developed an immunohistochemistry based test that enables us to take biopsies from patients and look at S15 expression both on the tumor as well as looking at the M2 macrophages within the stroma.
So we think this gives us a real competitive advantage to enrich for those patient cohorts that we believe will be most responsive to therapy. This was not an easy undertaking. And as many of you know, it's taken a little bit longer than anticipated. This started with the work in collaboration with David Rem, a leading pathologist at Yale, where we screen many monoclonal antibodies with respect to murine, rabbit and other types of monoclonals. And through that effort, we were able to define a specific 1 that gave us the specificity and the sensitivity.
Once that was done, we then needed to work closely with our CRO to do additional development of the assay and the validation. Long term process, the nice thing is we've been applying the same process now for NC410 and NC762. So to answer your question, the test is ready to go. We're in the process of submitting an amendment to the FDA. Hopefully, we'll hear back shortly and we'll start screening patients and look for those S15 positive individuals.
Okay, great. And maybe you could talk a little bit about the investigator led study at Yale. It's going to be NC318 in non small cell lung and it will test obviously monotherapy but also in combination small cell lung cancer, given the Phase I data and sort of small cell lung cancer given the Phase I data? And sort of your thoughts around patients selection, I think, in terms of patient selection for this in terms of prior PD-one exposure?
Yes. Thanks, Alex. So There was a little bit of a delay. Yes, so with respect to the Phase I study where we saw the PR and CR in 3 stable disease in non small cell lung cancer, that gave us hope that moving forward we would be able to treat this population. Unfortunately, when we enrolled lung cancer patients in the Phase 2 component, we did not see any responses.
When we went back and looked at the biopsies, we saw very few patients that were S15 positive. So at that point, that led us to believe that S15 selection was going to be more important. So during middle of last year, we put lung cancer on hold. We were moving forward with head and neck as well as triple negative breast cancer where we saw PRs in each of those indications. So through our founding institution Yale, where they were involved is a site in the Phase 1 study, They remain very interested in SigV-fifteen biology.
We got to know Roy Herbst and Scott Geninger quite well, leading lung cancer specialists, And they were interested in doing a NC318 study in combination with pembroke based on some of the preclinical data that we have generated in combination with anti PD-one. So based on that, coupled with a very clear design that our CMO, Hahn Ment and his team have been focused on in collaboration with our colleagues at Yale. We have a real great strategy to move forward. It has a monotherapy arm where we will select for S15 positive patients. These will be PD-one refractory patients.
And then there'll be 2 arms with respect to the combination with pembroke where we'll be focused on refractory and naive patients. So we think this is a kind of a very important move for the company in not giving up on lung. We still believe that both the preclinical data, all of the immunohistochemistry expression data coupled with the Phase 1 data that we've observed and CD13 is playing a very important role and working through our Phase 2 and now working with Yale, we'll be able to answer some of these key questions in monotherapy in combination with pembro and then also applying an extensive biomarker analysis. So there's a lot of traditional work in immunophenotyping, looking at cytokines and chemokines. We'll be looking at soluble Signet-fifteen, which could be playing an important role in the mechanism of action.
We'll be applying NanoString technology. So we'll be able to look at both tissue and things within the blood to determine mechanistically is MT-three 18 doing what it needs to do.
Okay. That makes sense. And maybe switching over to NC410, obviously, Layer 1 is another novel target that hasn't really been pursued by many others. So could you maybe just talk about Layer 1, your rationale for going after this molecule and sort of the preclinical observations that have supported your confidence going into the Phase 1 study?
Yes. So LARE-one has been around for a while. It was first discovered in the context of autoimmunity by Lindy Maynard, who's actually 1 of our collaborators at the University of Utrecht now. Liping and our Head of Discovery, Dallas Police, actually worked on LARE-one many years ago, because it's a co inhibitory molecule similar to other immune modulators that people are evaluating. The layer 1 biology is quite exquisite because it's a natural process in which a tumor has hijacked the immune system to prevail.
So layer 1, as we were describing earlier, is expressed on T cells and dendritic cells. And by binding 1 of ligands either collagen on the tumor or C1q, which is part of the complement pathway, you have a negative signaling effect, which creates an immunosuppressive condition in the TME and when that allows the tumor to grow. Somewhere along the way, mother nature duplicated the layer 1 gene to create layer 2. It's 70% homologous to layer 1, but it differs in 2 respects. It's soluble, so it's not membrane bound and it binds to collagen and C1P with higher affinity.
So what we've done in creating NC410 is this bio mimic that works as a decoy similar to layer 2 to basically counteract layer 1 binding to its ligands enabling us to activate the T cells and dendritic cells to restore immune function. So the preclinical data that we've generated mechanistically has demonstrated that this works exactly the way mother nature probably intended for it to do. We've generated a significant amount of in vivo data to demonstrate the biological activity and the function of NC410. But I think quite interestingly is some of the combo data that we reported on at SITC last year. We presented 2 posters, 1 on the mechanism of action of NC410.
And 2 was the collaboration we've had with NCI, where we were looking at Bintra, which is a PD L1 TGF beta trap in combination with NC410. And we saw exquisite and impressive tumor killing in those experiments. Quite interestingly, when we went back to challenge the mice, they maintained a memory immune response and the tumors did not come back. We actually repeated the findings internally here next year with PD L1. And then thirdly, also with our collaborator in the Netherlands.
So in 3 independent studies, we've seen very important combination study of NC410 with a PD L1 like molecule. And what we believe is happening is you're changing the extracellular matrix architecture. And by doing that, it may enable PD L1 to do certain things beyond what it might be able to do on its own and seeing this synergistic effect. So we're learning a lot about the biology of LAYER-one. We think NC410 has some real special properties from a functional perspective.
And now we're really excited as we work through the Phase 1 dose escalation study. We're about midway through the cohorts. And as I mentioned, we'll be reporting an update on that trial by year end.
Okay. That makes sense. We're definitely looking forward to the data update later this year. I think you said that we may be seeing some data from 4.10 at ASCO as well. I think I heard you right.
Yes. So this is basically will just be pretty much a trial update on trial and progress. So we'll provide some additional preclinical data as well as kind of a design of the trial. And this is being shared kind of in anticipation of the more focused clinical data to your end.
Okay. All right. That makes sense. And maybe switching over now to NC 762, which is your newest asset. Should we assume that the Phase 1 will be structured sort of similarly to MC318 and MC MC410?
Obviously, your view planning to include selection maybe from the get go in this study as well?
Yes. So I'm looking at MT762 focused on B7 H4. Yes, the trial design is pretty similar to what we've seen. It's pretty much a 3 by 3 design. It's a dose escalation study looking at safety and tolerability.
Obviously, we'll be looking very closely at clinical samples that we could evaluate from a biomarker perspective. But mainly, we're looking at safety and a recommended Phase 2 dose that we could then move forward with a Phase 2 where we will be using a CLIA validated test to select those patients that are expressing B7 H4 and that we think will be most responsive to NT762. Okay. I guess
if you look at the sort of expression patterns of B7 H4, are there any sort of tumor types that jump out that might be more amenable to treatment? I guess, sort of along those lines, I mean, B7H4 is also expressed in some autoimmune diseases as well. So are there any plans to maybe apply NC762 to those indications?
Yes. It's a great question. So V774 is over expressed in a number of different tumor types. People have worked on it for a fairly many, many years. I think our molecule has a unique mechanism of action and approach.
It's overexpressed in many gynecological cancers. So you see it really light up when you do the immunohistochemistry studies in breast cancer, in ovarian cancer, fallopian tube cancer. And of course, you see it in other types of cancers such as non small cell lung cancer. So we think this has a unique opportunity. I think the mechanism of action with respect to direct tumor killing is somewhat differentiated and enables us to kind of position this in monotherapy.
With that said, we will evaluate combinations if that makes sense from a lifecycle management. There are others working in the field looking at ADC types of approaches. If need be, we can certainly add a linker and a payload to it. But at this point, we don't think we need this to see the clinical effects. So we're obviously looking forward to starting that trial and getting that into patients to see what clinical impact it will have.
Okay. That makes sense. And maybe just wrapping up, you guys have alluded to plans to file at least 1 IND a year over the next few years. So the early stage pipeline is definitely not standing So maybe that would be great if you could provide a little bit more color on the preclinical work you guys have been doing and whether any of these INDs over the next few years could actually be maybe outside of oncology, say, and from 5AI or FindMind, there's the plan really just to go forward to answer?
Yes. So we've been developing our platform Find. Io platform We have a richness of assets. Each of these targets, We have a richness of assets. Each of these targets are novel, 1st in class and proprietary.
Each of these targets has a functional activity that impacts the immune system, so it can be stimulatory or inhibitory. And when we look at these targets, many of them are over expressed on tumors or various immune cells. But we've also learned over the years that some of these targets will have applications in like autoimmunity or neuro. And I know you sorry, you did mention autoimmunity in the case of B7 H4. And yes, there is applicability with respect to a fusion protein that could have impact on T cell mediated autoimmune diseases.
So we're very interested in looking at the other side of the immune system and this screening platform that we've developed enables us to look at these targets in a different way. Very similar to CTLA-four where the antibody focuses on cancer and the fusion protein AUREZYA focuses on arthritis. So we're always looking at that both sides of the pathway with respect to a ligand and a receptor and whether we want to develop an agonist and or antagonist to turn on the immune system or to turn it off in the case of autoimmunity. Neuro is a really interesting area. So we're very interested in looking at the convergence of neuroscience and inflammatory disease.
And many of the targets that we pull out of our screens, Alec, when we go back to the literature, you find out that they have roots in neuroscience or in some cases, even skeletal biology. And we think this is really interesting because before we had modern day immune systems, we had skeletal systems and we had neuro systems. So a lot of these targets that we've identified, we hope will have the opportunity to look at this kind of next wave of unmet medical need and looking at CNS disorders. And we hope to have some of these targets play a role in that.
Okay. Very interesting. Looking forward, definitely see the pipeline progress and enter the data later this year. So I think we're out of time, so we'll leave it there for today. But Mike, I really wanted to thank you for taking the time to participate in the conference and for the great overview of your business.
Really appreciate it.
Well, thank you very much, Alex. It's been a real pleasure and thanks for sharing your great questions and giving us this opportunity.
Of course. All right. Take care. And thanks to everyone on the line for your interest. All right.
Take care.
Thanks. Bye bye.